Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials

Authors: Chao Liu, Zhi Mao, Hongjun Kang, Jie Hu, Feihu Zhou

Published in: Critical Care | Issue 1/2016

Login to get access

Abstract

Background

Regional citrate or heparin is often prescribed as an anticoagulant for continuous renal replacement therapy (CRRT). However, their efficacy and safety remain controversial. Therefore, we performed this meta-analysis to compare these two agents and to determine whether the currently available evidence is sufficient and conclusive by using trial sequential analysis (TSA).

Methods

We searched for relevant studies in PubMed, Embase, the Cochrane Library databases and the China National Knowledge Infrastructure (CNKI) Database from database inception until September 2015. We selected randomized controlled trials comparing regional citrate with heparin in adult patients with acute kidney injury (AKI) who were prescribed CRRT.

Results

Fourteen trials (n = 1134) met the inclusion criteria. Pooled analyses showed that there was no difference in mortality between the regional citrate and heparin groups (relative risk (RR) 0.97, 95 % confidence interval (CI) 0.84, 1.13, P > 0.05), which was confirmed by TSA. Compared with heparin, regional citrate significantly prolonged the circuit life span in the continuous venovenous haemofiltration (CVVH) subgroup (mean difference (MD) 8.18, 95 % CI 3.86, 12.51, P < 0.01) and pre-dilution subgroup (MD 17.51, 95 % CI 9.85, 25.17, P < 0.01) but not in the continuous venovenous haemodiafiltration (CVVHDF) subgroup (MD 28.60, 95 % CI −3.52, 60.73, P > 0.05) or post-dilution subgroup (MD 13.06, 95 % CI −2.36, 28.48, P > 0.05). However, the results were not confirmed by TSA. A reduced risk of bleeding was found in the regional citrate compared with the systemic heparin group (RR 0.31, 95 % CI 0.19, 0.51, P < 0.01) and TSA provided conclusive evidence. Fewer episodes of heparin-induced thrombocytopoenia (HIT) (RR 0.41, 95 % CI 0.19, 0.87, P = 0.02) and a greater number of episodes of hypocalcaemia (RR 3.96, 95 % CI 1.50, 10.43, P < 0.01) were found in the regional citrate group. However, TSA did not provide conclusive evidence.

Conclusion

In adult patients with AKI, there is no difference in mortality between the regional citrate and heparin treated groups. However, regional citrate is more efficacious in prolonging circuit life span and reducing the risk of bleeding and should be recommended as the priority anticoagulant for critically ill patients who require CRRT.
Appendix
Available only for authorised users
Literature
1.
2.
Davenport A. What are the anticoagulation options for intermittent hemodialysis? Nat Rev Nephrol. 2011;7(9):499–508.PubMed
3.
Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy–heparin or citrate? Crit Care. 2011;15(1):202.CrossRefPubMedPubMedCentral
4.
Pinnick RV, Wiegmann TB, Diederich DA. Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med. 1983;308(5):258–61.CrossRefPubMed
5.
6.
Balogun RA, Turgut F, Caldwell S, Abdel-Rahman EM. Regional citrate anticoagulation in critically ill patients with liver and kidney failure. J Nephrol. 2012;25(1):113–9.CrossRefPubMed
7.
Lanckohr C, Hahnenkamp K, Boschin M. Continuous renal replacement therapy with regional citrate anticoagulation: do we really know the details? Curr Opin Anaesthesiol. 2013;26(4):428–37.CrossRefPubMed
8.
Wu MY, Hsu YH, Bai CH, Lin YF, Wu CH, Tam KW. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials. Am J Kidney Dis. 2012;59(6):810–8.CrossRefPubMed
9.
Zhang Z, Hongying N. Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med. 2012;38(1):20–8.CrossRefPubMed
10.
Liao YJ, Zhang L, Zeng XX, Fu P. Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy. Chin Med J (Engl). 2013;126(7):1344–9.
11.
Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, et al. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care. 2015;19:91.CrossRefPubMedPubMedCentral
12.
Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R. A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults. Crit Care Med. 2015;43(8):1622–9.CrossRefPubMed
13.
Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, et al. Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial. Crit Care. 2014;18(4):472.CrossRefPubMedPubMedCentral
14.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–41.CrossRefPubMed
15.
Guyatt GH, Oxman AD, Schunemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology. J Clin Epidemiol. 2011;64(4):380–2.CrossRefPubMed
16.
17.
Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9.CrossRefPubMedPubMedCentral
18.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.CrossRefPubMedPubMedCentral
19.
Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2008;61(1):64–75.CrossRefPubMed
20.
21.
Thorlund K, Devereaux PJ, Wetterslev J, Guyatt G, Ioannidis JP, Thabane L, et al. Can trial sequential monitoring boundaries reduce spurious inferences from meta-analyses? Int J Epidemiol. 2009;38(1):276–86.CrossRefPubMed
22.
Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol. 2009;9:86.CrossRefPubMedPubMedCentral
23.
Thorlund K EJ, Wetterslev J, Brok J, Imberger G, Gluud C. User manual for trial sequential analysis (TSA). In Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark; 2011: p.1–115. Available from www.​ctu.​dk/​tsa.
24.
Betjes MG, van Oosterom D, van Agteren M, van de Wetering J. Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding: similar hemofilter survival but significantly less bleeding. J Nephrol. 2007;20(5):602–8.PubMed
25.
Brain MJ, Roodenburg OS, Adams N, McCracken P, Hockings L, Musgrave S, et al. Randomised trial of software algorithm driven regional citrate anticoagulation versus heparin in continuous renal replacement therapy: the Filter Life in Renal Replacement Therapy pilot trial. Crit Care Resusc. 2014;16(2):131–7.PubMed
26.
Fealy N, Baldwin I, Johnstone M, Egi M, Bellomo R. A pilot randomized controlled crossover study comparing regional heparinization to regional citrate anticoagulation for continuous venovenous hemofiltration. Int J Artif Organs. 2007;30(4):301–7.PubMed
27.
Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P. Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Intensive Care Med. 2004;30(2):260–5.CrossRefPubMed
28.
Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, et al. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009;37(2):545–52.CrossRefPubMed
29.
Lin X, Qin Z, Chen L, Bu H. The comparing of anticoagulation with sodium citrate or heparin in continuous venovenous hemodiafiltration. Chin J Pract Intern Med. 2007;S1:194–6.
30.
Cui W, Deng X, Lv S, Hu Q, Zhang K. The observation on the comprehensive effect of extracorporeal citrate anticoagulation protocol in continuous blood purification. J Qiqihar Univ Med. 2011;12:1884–6.
31.
Yang S, Deng Q, Li B, Xiao Y. Comparison of anticoagulation using regional heparin, citrate and low molecular weight heparins forcontinuous renal replacement therapy in critically ill patients. J China-Japan Friendship Hosp. 2014;04:208–11.
32.
Tiranathanagul K, Jearnsujitwimol O, Susantitaphong P, Kijkriengkraikul N, Leelahavanichkul A, Srisawat N, et al. Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration. Ther Apher Dial. 2011;15(6):556–64.CrossRefPubMed
33.
Hetzel GR, Schmitz M, Wissing H, Ries W, Schott G, Heering PJ, et al. Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant. 2011;26(1):232–9.CrossRefPubMed
34.
Kutsogiannis DJ, Gibney RT, Stollery D, Gao J. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int. 2005;67(6):2361–7.CrossRefPubMed
35.
Cohen JF, Korevaar DA, Wang J, Spijker R, Bossuyt PM. Should we search Chinese biomedical databases when performing systematic reviews? Syst Rev. 2015;4:23.CrossRefPubMedPubMedCentral
36.
Baldwin I. Factors affecting circuit patency and filter 'life'. Contrib Nephrol. 2007;156:178–84.CrossRefPubMed
37.
Wu B, Zhang K, Xu B, Ji D, Liu Z, Gong D. Randomized controlled trial to evaluate regional citrate anticoagulation plus low-dose of dalteparin in continuous veno-venous hemofiltration. Blood Purif. 2015;39(4):306–12.CrossRefPubMed
38.
Slowinski T, Morgera S, Joannidis M, Henneberg T, Stocker R, Helset E, et al. Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study. Crit Care. 2015;19:349.CrossRefPubMedPubMedCentral
39.
Nurmohamed SA, Jallah BP, Vervloet MG, Yldirim G, ter Wee PM, Groeneveld AB. Continuous venovenous haemofiltration with citrate-buffered replacement solution is safe and efficacious in patients with a bleeding tendency: a prospective observational study. BMC Nephrol. 2013;14:89.CrossRefPubMedPubMedCentral
40.
Morgera S, Scholle C, Voss G, Haase M, Vargas-Hein O, Krausch D, et al. Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience. Nephron Clin Pract. 2004;97(4):c131–136.CrossRefPubMed
41.
Park JS, Kim GH, Kang CM, Lee CH. Regional anticoagulation with citrate is superior to systemic anticoagulation with heparin in critically ill patients undergoing continuous venovenous hemodiafiltration. Korean J Intern Med. 2011;26(1):68–75.CrossRefPubMedPubMedCentral
42.
Schilder L, Nurmohamed SA, ter Wee PM, Paauw NJ, Girbes AR, Beishuizen A, et al. The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied. Crit Care. 2014;18(2):R78.CrossRefPubMedPubMedCentral
43.
Schilder L, Nurmohamed SA, ter Wee PM, Paauw NJ, Girbes AR, Beishuizen A, et al. Citrate confers less filter-induced complement activation and neutrophil degranulation than heparin when used for anticoagulation during continuous venovenous haemofiltration in critically ill patients. BMC Nephrol. 2014;15:19.CrossRefPubMedPubMedCentral
44.
Feltes CM, Van Eyk J, Rabb H. Distant-organ changes after acute kidney injury. Nephron Physiol. 2008;109(4):80–4.CrossRef
Metadata
Title
Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials
Authors
Chao Liu
Zhi Mao
Hongjun Kang
Jie Hu
Feihu Zhou
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1299-0

Other articles of this Issue 1/2016

Critical Care 1/2016 Go to the issue

Review

Predicting cardiorespiratory instability

Research

Use of CRB-65 and quick Sepsis-related Organ Failure Assessment to predict site of care and mortality in pneumonia patients in the emergency department: a retrospective study

Letter

Impact of documentation on interpretation of administrative data

Research

Use of intra-osseous access in adults: a systematic review

Research

Surviving critical illness: what is next? An expert consensus statement on physical rehabilitation after hospital discharge

Research

Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest – an analysis of the TTM trial data